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PubMed2005

Renocortical mRNA expression of vasoactive factors during spironolactone protective effect in chronic cyclosporine nephrotoxicity.

We showed that spironolactone reduced structural damage and prevented renal dysfunction in chronic cyclosporine (CsA) nephrotoxicity. These findings evidenced an aldosterone renal vascular effect under this condition. To investigate aldosterone's role in modulating renal vascular tone, renocortical vasoactive pathways mRNA levels in chronic CsA nephrotoxicity as well as spironolactone's effect on renal function in acute CsA nephrotoxicity were evaluated. Two experimental sets were designed. For chronic nephrotoxicity, rats fed with low-sodium diet were divided into groups receiving vehicle, spironolactone (Sp), CsA, and CsA+Sp, for 21 days. Creatinine clearance, survival percentage, and renocortical mRNA levels of pro-renin, angiotensinogen (Ang), angiotensin receptors (AT(1A), AT(1B), and AT(2)), preproendothelin, endothelin receptors (ET(A), ET(B)), cyclooxygenase-2 (COX-2), and adenosine receptors (Ad(1), Ad(2A), Ad(2B), and Ad(3)) were analyzed. For acute nephrotoxicity, similar groups fed with a standard chow diet for 7 days were included. Serum potassium and sodium, glomerular filtration rate (GFR), and renal blood flow (RBF) were determined. In chronic model, CsA produced pro-renin and ET upregulation, altered adenosine receptors expression, and reduced Ang, AT(1A), AT(1B), ET(B), and COX-2 mRNA levels. Spironolactone protective effect in chronic nephrotoxicity was associated with prevention of pro-renin upregulation and increased AT(2), together with ET(B) reduction. In acute nephrotoxicity, spironolactone completely prevented GFR and RBF reduction induced by CsA. Our results suggest that aldosterone contributes to renal vasoconstriction observed in CsA nephrotoxicity and that renoprotection conferred by spironolactone was related to modification of renocortical vasoactive pathways expression, in which pro-renin normalization was the most evident change in chronic nephropathy. Finally, our data point to spironolactone as a potential treatment to reduce CsA nephrotoxicity in transplant patients.

Aldosterone↗
PubMed2005

Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001.

BACKGROUND: Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure. METHODS AND RESULTS: This is a study of serial cross-sectional samples of Medicare beneficiaries > or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction. The first sample was discharged before (April 1998 to March 1999, n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication of RALES in September 1999. We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial. Using multivariable logistic regression, we identified factors independently associated with prescriptions not meeting these criteria. Spironolactone use increased >7-fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment criteria, 24.1% received spironolactone, as compared with 17.4% of those not meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8% of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In multivariable analyses, factors associated with prescriptions not meeting enrollment criteria included advanced age, noncardiovascular comorbidities, discharge to skilled nursing facilities, and care provided by physicians without board certification. CONCLUSIONS: Spironolactone prescriptions increased markedly after the publication of RALES, and many treated patients were at risk for hyperkalemia. Simultaneously, many patients who might have benefited were not treated. These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events.

Aged↗
PubMed1997

Spironolactone-induced agranulocytosis.

OBJECTIVE: To report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 x 10(3)/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 x 10(3)/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drug dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.

Agranulocytosis↗
PubMed2006

Protective effect of spironolactone on endothelial cell apoptosis.

Human umbilical vein endothelial cells (HUVECs) undergo apoptosis in response to serum deprivation. We show that the nonspecific mineralocorticoid receptor antagonist, spironolactone, protects from caspase-3 activation induced by serum deprivation in contrast to the selective mineralocorticoid receptor antagonist, eplerenone, that is nonprotective. We also demonstrate that progesterone, hydrocortisone, and dexamethasone all protect HUVECs from serum-deprivation-induced caspase-3 activation, whereas aldosterone and dihydrotestosterone have no effect. Spironolactone has been demonstrated to display agonist activity only to the progesterone receptor (PR), and we additionally show that spironolactone and progesterone, but not eplerenone, inhibit mitochondrial cytochrome c release and cleavage of nuclear poly (ADP-ribose) polymerase (PARP) and increase cell viability. Additionally, the PR antagonist mifepristone (RU486) partially blocked the inhibitory effect of both spironolactone and progesterone on caspase-3 activation, cytochrome c release, and nuclear PARP cleavage. Nitric oxide (NO) protects HUVECs from apoptosis in response to various stimuli including serum-deprivation; however, the NO synthase inhibitor N-monomethyl-l-arginine, did not abolish inhibition of caspase-3 activation or PARP cleavage by spironolactone. Thus, we demonstrate that spironolactone protects HUVECs from serum-deprivation-induced apoptosis by inhibition of caspase-3 activity, cytochrome c release and PARP cleavage by a NO-independent mechanism; further, this effect is likely mediated by the agonist properties of spironolactone toward the PR.

Aldosterone↗
PubMed1988

Side-effects of spironolactone therapy in the hirsute woman.

Spironolactone, an aldosterone antagonist with antiandrogenic activities, is often used to treat hirsute women. Several investigators have reported beneficial effects of such treatment, but the dosages used and side-effects encountered differ in their reports. To clarify this issue, 26 consecutive premenopausal women with idiopathic hirsutism were prospectively evaluated during spironolactone treatment. Sixteen women initially received 100 mg spironolactone twice daily on days 4-21 of their menstrual cycles. In 11 women (68%), the dosage had to be decreased or the medication discontinued due to side-effects. The major side-effect, metrorrhagia with 14-day cycles, occurred in 9 women (56%). This side-effect, while not dangerous, was intolerable to these women. In one woman, spironolactone was discontinued because of urticaria and in another because of scalp hair loss. Ten women initially received 50 mg spironolactone twice daily on days 4-21 of their menstrual cycles. Two developed metrorrhagia, but no other side-effects were noted. Because of the incidence of metrorrhagia at higher dosages, we recommend that spironolactone be administered cyclically at a starting dosage of 50 mg twice daily on days 4-21 of the menstrual cycle. Alternatively, one may consider adding cyclical estrogen/progesterone therapy to continuous spironolactone therapy.

Adult↗
PubMed2004

Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis.

Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticoid receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (1 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9+/-49.2 mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0+/-4.0 mg/day, p=0.0046) and the cilazapril-treated group (71.8+/-26.0 mg/day, p=0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4+/-4.5 mg/day, p=0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0+/-18.4 vs. 80.3+/-18.5 in the untreated group, p=0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1980

Interaction of spironolactone with oestradiol receptors in cytosol.

The role of spironolactone in the aetiology of gynaecomastia was examined in terms of its ability to bind to the oestrogen receptor in cytosol, to cause specific oestrogenic effects in the absence of endogenous oestrogen and to be antioestrogenic in the presence of oestradiol. Tamoxifen, a non-steroidal antioestrogen, was chosen as an internal standard for comparison. Spironolactone and tamoxifen competitively inhibited the binding of oestradiol-17beta to its receptor in uterine and mammary cytosol, with inhibition constants of 2 x 10(-5) and 1 x 10(-7) mol/l respectively. To measure oestrogenic or antioestrogenic effects of the drugs five indices believed to be specific markers for oestrogen action were studied: uterine to body weight ratio, uterine protein content, oestradiol receptor in cytosol, progesterone receptor in cytosol and uterine peroxidase activity. Spironolactone, when administered for 3 successive days (40 microgram/day) to immature female rats, increased all of the five indices of oestrogen agonistic activity. The oestrogen-antagonistic properties of the drug were evaluated by comparing the oestradiol-injected group (5 microgram) to the oestradiol + spironolactone-injected group. A decrease was noted in all indices measured except for progesterone receptors in cytosol. Spironolactone appeared to be very similar to tamoxifen in its action both as an oestrogen and as an antioestrogen. The antioestrogenic effect of spironolactone cannot be explained by previously proposed mechanisms of action for the drug such as decreased synthesis of testosterone or inhibition of dihydrotestosterone binding to its receptor. These results suggest that spironolactone-induced gynaecomastia may be modulated by its action at both the oestrogen and dihydrotestosterone receptor in cytosol.

Animals↗
PubMed2006

Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and proximal tubular cells. There were no changes in blood glucose concentration or BP after spironolactone treatment. Spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of MCP-1 were significantly increased concurrently with renal expression of MCP-1, macrophage migration inhibitory factor, and macrophage infiltration. Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as well as renal MCP-1 and migration inhibitory factor expression and macrophage infiltration. In addition, aldosterone induced upregulation of MCP-1 expression and NF-kappaB transcriptional activity in cultured cells, and spironolactone reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB inhibition abolished aldosterone-induced MCP-1 production. Overall, these findings suggest that aldosterone-induced NF-kappaB activation leads to activation of proinflammatory cytokines, ultimately leading to renal injury in this model. These data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy.

Animals↗
PubMed2002

[Bullous pemphigoid induced by spironolactone].

INTRODUCTION: The role of spironolactone as pemphigoid-inducing agent has recently been suggested. We report a new case of pemphigoid probably induced by spironolactone. The disease resolved after withdrawal of the diuretic drug containing aldactone. OBSERVATION: A 76 year-old patient was hospitalized for eczematiform lesions and severe pruritus. Histological and immunological investigations led to the diagnosis of pemphigoid. For several years, the patient had been treated with acarbose, amlodipine, fluvastatine, buflomedil, lysine acetylsalicylate and a spironolactone-furosemide association. On withdrawal of spironolactone alone, the cutaneous lesions regressed spontaneously within 15 days and no relapse was noted 30 months later. DISCUSSION: Numerous observations have suggested the role of certain drugs in the occurrence of pemphigoid. A recent test case study concerning drugs administered to patients suffering from pemphigoid has shown the significant association with spironolactone and neuroleptics. In our case report, the imputability of spironolactone is plausible. Because of the poor prognosis of pemphigoid, essentially due to iatrogenic complications, it is valuable to be able to delay the initiation of specific treatment for a few days, in patients receiving spironolactone.

Aged↗
PubMed1992

Interaction of spironolactone with mercury. A possible molecular mechanism.

The protective activity of spironolactone (CAS 52-01-7) against mercuric acetate intoxication and the action of a spironolactone-mercuric acetate complex were studied on female Sprague-Dawley rats. Spironolactone was given 30 min after the toxic agent. It was found that spironolactone reversed the toxic effects of mercury, the mercury-spironolactone complex was much less toxic than mercuric acetate and its toxicity disappeared with the administration of spironolactone. A molecular mechanism for the protective action of spironolactone against mercury intoxication is proposed. The presence of both the steroidal skeleton and the thioacetyl group in the same molecule is necessary for the protection against mercury intoxication.

Animals↗
PubMed2006

Eplerenone: new drug. Recent myocardial infarction with heart failure: a spironolactone me too.

(1) Heart failure is diagnosed on the basis of both clinical symptoms and evaluation of cardiac function (preferably measured by echocardiography). Left ventricular dysfunction is defined as a left ventricular ejection fraction (LVEF) below 40%. The drugs of choice for chronic heart failure are certain angiotensin-converting-enzyme (ACE) inhibitors, some diuretics, some betablockers, and spironolactone. In one trial, spironolactone greatly reduced mortality at 24 months (35%, compared with 46% on placebo, p <0.001). (2) Eplerenone, a spironolactone derivative, is marketed for the treatment of left ventricular dysfunction in heart failure patients with recent myocardial infarction. (3) The EPHESUS study, a double-blind, placebo-controlled trial involving 6632 patients, showed a significant reduction in the overall mortality rate among patients with heart failure and recent myocardial infarction treated with eplerenone for 16 months (16.7% versus 14.4%; p = 0.008). This improvement was mainly due to a reduction in mortality during the first month of treatment. Eplerenone has not been compared with spironolactone, although the latter was known to be effective before the EPHESUS trial was conducted. (4) Severe hyperkalemia is frequent with eplerenone, occurring in 5.5% of patients. The risk of hyperkalaemia increases with renal failure and co-administration of potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists and nonsteroidal antiinflammatory drugs. (5) In the short term, the incidence of gynecomastia in patients taking eplerenone seems to be low. (6) In patients who develop heart failure after myocardial infarction, an indirect comparison of available data favours spironolactone over eplerenone (better efficacy, lower risk of hyperkalemia). (7) In France, treatment with eplerenone is about 9 times more expensive than spironolactone. (8) Spironolactone remains the treatment of choice for patients with heart failure and incapacitating dyspnea despite ACE inhibitor and diuretic therapy. Eplerenone may possibly be useful for patients who have non severe heart failure after recent myocardial infarction.

Clinical Trials as Topic↗
PubMed2006

[Use of spironolactone and indapamide in the treatment of low-renin arterial hypertension].

AIM: To compare efficacy of use of the blocker of aldosteron receptors spironolactone and diuretic indapamide in low-renin arterial hypertension (AH), their action on blood pressure, serum concentrations of sodium, potassium, creatinine, plasmic renin activity (PRA), plasmic aldosteron concentration (PAC). MATERIAL AND METHODS: The study included 31 females aged 40-60 years with hardly correctable AH and high PAC to (PRA) ratio. Biochemical parameters were measured before 2-week treatment with indapamide (1.5 mg/day) and spironolactone (25 mg/day) and after the treatment. Between the courses there was a 2-week interval. RESULTS: In AH patients with high PAC/PRA spironolacton reduced AP more significantly (-15.5 / -8.2 mmHg) than indapamide (-10.9 / -5.9 mmHg). Indapamide lowered potassium serum levels by 0.28 mmol/l (p < 0.05), spironolacton raised it by 0.26 mmol/l (p = 0.05). Sodium concentration in the serum reduced only after treatment with spironolactone. Both drugs increased blood concentrations of creatinine, aldosteron, PRA, but spironolactone was more active. CONCLUSION: In treatment-resistant AH it is necessary to perform screening for detection of patients with low-renin hypertension. Such patients are effectively treated with spironolacton in low doses.

Adult↗
PubMed1991

Vascular and cardiac actions of aldosterone and spironolactone.

Classical pharmacology confines the mechanism of action of aldosterone and its antagonists to the modulation of ion transport in the distal tubule of the nephron. The purpose of this overview is to examine the evidence for the presence of extrarenal and, namely, vascular and cardiac sites of action for aldosterone and spironolactone. Beside its specific action in primary and secondary hyperaldosteronism, spironolactone is effective in lowering blood pressure in essential hypertension, despite normal levels of aldosterone production, and without necessarily producing significant changes in Na+ and K+ urinary excretion. This is particularly the case when therapy is applied chronically and at relatively low doses. This suggests that spironolactone may act by antagonizing the effects of aldosterone directly on the cardiovascular system. Electrophysiological studies have shown that spironolactone may reduce contractions of rat portal vein strips. This action was found to be mediated by the inhibition of the slow calcium channels. Spironolactone binds to the calcium channels, at sites different from those of dihydropyridines and phenylalkylamines. It interacts at these binding sites in vascular membranes by decreasing their density and accelerating the rate of dissociation of the ligand. In humans, spironolactone 50 mg and 75 mg o.d. produced a dose-dependent decrease of total vascular resistance and in vascular reactivity to vasopressor agents. In the heart, spironolactone produces a direct inotropic action in the mammalian myocardium with an increase of both the amplitude and duration of action potential. Finally, the direct role of aldosterone in promoting fibroblast growth producing cardiac hypertrophy in models of experimental hypertension have been recently emphasized.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1994

Comparison of the efficacy of spironolactone versus flutamide in the treatment of hirsutism.

OBJECTIVE: To compare the efficacy of two antiandrogens, spironolactone and flutamide, in the treatment of hirsutism. PATIENTS, PARTICIPANTS: Twenty women with idiopathic hirsutism were randomized to receive either flutamide or spironolactone. DESIGN: Twenty hirsute women were recruited from patients presenting to the hirsutism clinic in Marmara University, Istanbul. Each patient underwent a complete medical and gynecological examination as well as endocrine profile, hematologic, hepatic, and renal function analyses. Hirsutism scores were determined according to the Ferriman-Gallwey scoring system. These tests were then repeated at 3, 6, and 9 months of therapy. Ten patients received 250 mg of flutamide two times per day, and 10 patients received 100 mg of spironolactone for 9 months. RESULTS: Ferriman-Gallwey scores were decreased significantly in both groups at the end of 9 months. The percent of change in hirsutism scores in flutamide and spironolactone group were as follows: 26.4% and 20.9% at 3 months; 39.5% and 32.9% at 6 months; and 46.4% and 39.6% at 9 months, respectively. There was a trend toward a better response with flutamide that did not achieve significance. None of the hormonal parameters changed significantly during this period of time. Irregular bleeding was observed in five patients (50%) of the spironolactone group, whereas none of the patients in the flutamide group experienced menstrual irregularity. Conversely, dry skin and increased appetite were experienced by two patients (20%) in the flutamide group but not in the spironolactone group. CONCLUSION: These data suggest that both spironolactone and flutamide were similarly effective in treatment of hirsutism, and the pure antiandrogen flutamide is a safe and effective alternative in treatment.

Adolescent↗
PubMed1977

Validation of plasma and urinary canrenone for determination of bioavailability of spironolactone--comparison of tablets with solution/suspension.

Data showing a linear relationship between spironolactone dose and the levels of canrenone in plasma and urine are presented to support the use of canrenone levels as a measure of the bioavailability of spironolactone. The bioavailability of a selected batch of spironolactone 25 mg tablets was compared to that of an oral aqueous suspension of spironolactone in a separate balanced cross-over study involving 10 healthy subjects. The tablets were equivalent to suspension as regards area under the plasma concentration-time curve and total urinary excretion of canrenone, the prinicipal unconjugated metabolite of spironolactone. Peak plasma concentrations of canrenone were higher, and were attained significantly earlier, after treatment with spironolactone in suspension. The results indicate that spironolactone was absorbed more rapidly from the suspension, but that the total absorption did not differ between the two formulations.

Administration, Oral↗
PubMedDate not supplied

Effect of micronization on the bioavailability and pharmacologic activity of spironolactone.

The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of these tablets were identical. After 200-mg single doses, the bioavailability of micronized tablets was significantly higher than that of standard tablets. Furthermore, as assessed by 24-hour urine log10 10 Na/K ratio, the pharmacologic activity of micronized spironolactone was significantly greater than that of the standard formulation. The significant influence on renal antimineralocorticoid activity of raised plasma and urinary levels of canrenone, quantitatively the major active metabolite of spironolactone in man, emphasizes the clinical importance of the bioavailability of spironolactone preparations. Since this study, the process used in the manufacture of spironolactone (Aldactone) tablets has been under review.

Biological Availability↗
PubMed2006

A new enzyme-linked chemiluminescent immunosorbent digoxin assay is virtually free from interference of spironolactone, potassium canrenoate, and their common metabolite canrenone.

Spironolactone and potassium canrenoate (aldosterone antagonist diuretics) are sometimes used in conjunction with digoxin for patient management. Spironolactone, potassium canrenoate, and their common metabolite canrenone interfere with serum digoxin measurement using various immunoassays. Recently a new enzyme-linked chemiluminescent immunosorbent digoxin assay (ECLIA-Digoxin) became commercially available for application on the ADVIA IMS 800i modular system (Bayer HealthCare, Tarrytown, NY). We investigated the potential interference of spironolactone and related compounds in this assay by comparing the results with the fluorescence polarization immunoassay (FPIA), which is known to have significant cross-reactivity with these compounds as well as a turbidimetric assay for digoxin with no known cross-reactivity with spironolactone and related compounds. Aliquots of drug free serum were supplemented with therapeutic and above therapeutic concentrations of spironolactone, canrenone, and potassium canrenoate, and apparent digoxin concentrations were measured. No apparent digoxin concentration was observed using the ECLIA-Digoxin or turbidimetric assay. When serum pools prepared from patients receiving digoxin were further supplemented with these compounds, we observed no significant change in digoxin concentrations in the presence of these compounds with the ECLIA-Digoxin. We conclude that this assay is virtually free from interferences from spironolactone, potassium canrenoate and their common metabolite canrenone.

Artifacts↗
PubMed1982

Effect of spironolactone on systemic blood pressure, limb blood flow and response to sympathetic stimulation in hypertensive patients.

Since there is only scanty, indirect information about the mechanism of the hypotensive effect of spironolactone, 9 patients with essential hypertension were studied according to a randomised double-blind, cross-over protocol. Spironolactone 100mg b.i.d. and placebo were each given for one month and the following parameters were studied: blood pressure, heart rate, response to cold pressure and handgrip tests, as well as blood flow in the calf and finger vessels. Flow in the calf and fingers representing muscle and skin arteries, respectively, was measured semicontinuously with an ECG-triggered venous occlusion plethysmograph. After spironolactone there was a significant decrease in the systolic and diastolic blood pressures in the supine, sitting and standing positions; the sitting systolic and diastolic blood pressure decreased by (mean +/- SE) 27 +/- 4mm Hg (p less than 0.001) and 11 +/- 4mm Hg (p less than 0.02), respectively. No orthostatic response was observed. Heart rate remained unchanged. Blood flow through muscle and skin vessels increased in 6 out of 9 patients, and in these patients calculated vascular resistance in these areas decreased. Spironolactone did not significantly change the response of systemic blood pressure to the handgrip and cold pressure tests. The present data confirm the hypotensive properties of spironolactone and show that this effect is associated with dilatation of muscle and skin arteries in many but not in all the patients. The data do not support the hypothesis that spironolactone decreases the responsiveness of systemic blood pressure to orthosympathetic stimulation.

Blood Pressure↗